S258: LISOCABTAGENE MARALEUCEL (LISO-CEL) AS SECOND-LINE THERAPY FOR R/R LARGE B-CELL LYMPHOMA (LBCL) IN PATIENTS NOT INTENDED FOR HSCT: PRIMARY ANALYSIS FROM THE PHASE 2 PILOT STUDY
Authors: A. Sehgal, D. Hoda, P. A. Riedell, N. Ghosh, M. Hamadani, G. C. Hildebrandt, J. E. Godwin, P. Reagan, N. Wagner-Johnston, J. Essell, R. Nath, S. R. Solomon, R. Champion, E. Licitra, S. Fanning, N. Gupta, R. Dubowy, A. D’Andrea, L. Wang, L. I. Gordon
Journal: HemaSphere (2022)

Background: Patients with relapsed or refractory (R/R) LBCL after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. Aims: PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as second-line treatment in patients with R/R LBCL not intended for HSCT. Methods: Eligible patients were adults with R/R LBCL after first-line treatment who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 2, diffusing capacity for carbon monoxide ≤ 60%, left ventricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Bridging therapy was allowed. Patients received lymphodepletion with cyclophosphamide and fludarabine, followed 2–7 days later by liso-cel infusion at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Neurological events (NE) were defined as investigator-identified neurological adverse events related to liso-cel and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. The primary endpoint was objective response rate (ORR) per independent review committee; all patients had ≥ 6 months of follow-up from first response. Results: Of 74 patients who underwent leukapheresis, 61 received liso-cel and 1 received nonconforming product (ie, product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered liso-cel). Common reasons for preinfusion dropout included death and loss of eligibility (5 each). For liso-cel–treated patients, median age was 74 years (range, 53–84; 79% ≥ 70 years) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively; 26% had ECOG PS of 2 and 44% had Hematopoietic Cell Transplantation-specific Comorbidity Index score ≥ 3. After first-line treatment, 54% were chemotherapy refractory, 21% relapsed within 12 months, and 25% relapsed after 12 months; 51% of patients received bridging chemotherapy. Median (range) on-study follow-up was 12.3 months (1.2–26.5). ORR and complete response rate were 80% and 54%, respectively (Table). Median duration of response and progression-free survival were 12.1 months and 9.0 months, respectively. Median overall survival has not been reached. The most frequent treatment-emergent adverse events (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade 3 CRS in 1 patient (2%) and no grade 4/5 CRS events. Any-grade NEs were seen in 31% (n = 19) of patients; grade 3 NEs occurred in 5% (n = 3) of patients and no grade 4/5 NEs were reported. Seven percent (n = 4) received tocilizumab only, 3% (n = 2) received corticosteroids only, and 20% (n = 12) received both tocilizumab and corticosteroids for treatment of CRS and/or NEs. Overall, grade ≥ 3 TEAEs occurred in 79% (n = 48) of patients, with grade 5 TEAEs in 2 patients (both due to COVID-19). Two patients (3%) had grade 3/4 infections and 15 (25%) had grade ≥3 neutropenia at Day 29. Image:Summary/Conclusion: In the PILOT study, liso-cel as second-line treatment in patients with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns.